ID SPSB2_MOUSE Reviewed; 264 AA. AC O88838; Q8CBA5; Q91Z15; DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 22-APR-2020, entry version 146. DE RecName: Full=SPRY domain-containing SOCS box protein 2; DE Short=SSB-2; DE AltName: Full=Gene-rich cluster protein C9; GN Name=Spsb2; Synonyms=Grcc9, Ssb2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9445485; RA Ansari-Lari M.A., Oeltjen J.C., Schwartz S., Zhang Z., Muzny D.M., Lu J., RA Gorrell J.H., Chinault A.C., Belmont J.W., Miller W., Gibbs R.A.; RT "Comparative sequence analysis of a gene-rich cluster at human chromosome RT 12p13 and its syntenic region in mouse chromosome 6."; RL Genome Res. 8:29-40(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Friedel E.J., Nicholson S.E., Nicola N.A., Kile B.T., Hilton D.J.; RT "SOCS box proteins."; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Bone; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC STRAIN=FVB/N; TISSUE=Mammary gland, and Mammary tumor; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, INTERACTION WITH NOS2, AND MUTAGENESIS OF 100-ARG-GLY-101; RP 102-THR-HIS-103; 118-ASP-HIS-119; TYR-120; 123-LEU--GLY-125; RP 126-SER--SER-128; 160-GLN-LEU-161; VAL-206 AND TRP-207. RX PubMed=20603330; DOI=10.1083/jcb.200912087; RA Kuang Z., Lewis R.S., Curtis J.M., Zhan Y., Saunders B.M., Babon J.J., RA Kolesnik T.B., Low A., Masters S.L., Willson T.A., Kedzierski L., Yao S., RA Handman E., Norton R.S., Nicholson S.E.; RT "The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for RT proteasomal degradation."; RL J. Cell Biol. 190:129-141(2010). RN [6] RP INTERACTION WITH PAWR, AND MUTAGENESIS OF TYR-120; 123-LEU--GLY-125; RP 126-SER--SER-128; THR-198 AND VAL-206. RX PubMed=20561531; DOI=10.1016/j.jmb.2010.06.017; RA Filippakopoulos P., Low A., Sharpe T.D., Uppenberg J., Yao S., Kuang Z., RA Savitsky P., Lewis R.S., Nicholson S.E., Norton R.S., Bullock A.N.; RT "Structural basis for Par-4 recognition by the SPRY domain- and SOCS box- RT containing proteins SPSB1, SPSB2, and SPSB4."; RL J. Mol. Biol. 401:389-402(2010). RN [7] RP STRUCTURE BY NMR OF 12-224, INTERACTION WITH PAWR AND MET, AND MUTAGENESIS RP OF TYR-120; 123-LEU--GLY-125; 141-TYR--GLN-143; 151-GLN-TYR-152; RP 188-GLY-PRO-189 AND VAL-206. RX PubMed=16369487; DOI=10.1038/nsmb1034; RA Masters S.L., Yao S., Willson T.A., Zhang J.-G., Palmer K.R., Smith B.J., RA Babon J.J., Nicola N.A., Norton R.S., Nicholson S.E.; RT "The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par- RT 4-binding residues."; RL Nat. Struct. Mol. Biol. 13:77-84(2006). CC -!- FUNCTION: Substrate recognition component of a SCF-like ECS (Elongin CC BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which CC mediates the ubiquitination and subsequent proteasomal degradation of CC target proteins (PubMed:20603330). Negatively regulates nitric oxide CC (NO) production and limits cellular toxicity in activated macrophages CC by mediating the ubiquitination and proteasomal degradation of NOS2 CC (PubMed:20603330). Acts as a bridge which links NOS2 with the ECS E3 CC ubiquitin ligase complex components ELOC and CUL5 (By similarity). CC {ECO:0000250|UniProtKB:Q99619, ECO:0000269|PubMed:20603330}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Component of the probable ECS(SPSB2) E3 ubiquitin-protein CC ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and CC SPSB2 (By similarity). Interacts with CUL5, RNF7, ELOB and ELOC (By CC similarity). Interacts with MET (PubMed:16369487). Interacts (via CC B30.2/SPRY domain) with PAWR; this interaction occurs in association CC with the Elongin BC complex (PubMed:16369487, PubMed:20561531). CC Interacts with NOS2. {ECO:0000250|UniProtKB:Q99619, CC ECO:0000269|PubMed:16369487, ECO:0000269|PubMed:20561531, CC ECO:0000269|PubMed:20603330}. CC -!- INTERACTION: CC O88838; Q96IZ0: PAWR; Xeno; NbExp=6; IntAct=EBI-8820410, EBI-595869; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:Q99619}. Note=Exhibits a diffuse cytosolic CC localization. {ECO:0000250|UniProtKB:Q99619}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O88838-1; Sequence=Displayed; CC Name=2; CC IsoId=O88838-2; Sequence=VSP_018613; CC -!- DOMAIN: The SOCS box domain mediates the interaction with the Elongin CC BC complex, an adapter module in different E3 ubiquitin ligase CC complexes (By similarity). Essential for its ability to link NOS2 and CC the ECS E3 ubiquitin ligase complex components ELOC and CUL5 (By CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q99619}. CC -!- SIMILARITY: Belongs to the SPSB family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AC002397; AAC36017.1; -; Genomic_DNA. DR EMBL; AF403037; AAL57356.1; -; mRNA. DR EMBL; AK036451; BAC29435.1; -; mRNA. DR EMBL; AK148177; BAE28397.1; -; mRNA. DR EMBL; BC002005; AAH02005.1; -; mRNA. DR EMBL; BC010305; AAH10305.1; -; mRNA. DR CCDS; CCDS20529.1; -. [O88838-1] DR RefSeq; NP_001292979.1; NM_001306050.1. [O88838-1] DR RefSeq; NP_001292980.1; NM_001306051.1. [O88838-1] DR RefSeq; NP_001292981.1; NM_001306052.1. [O88838-1] DR RefSeq; NP_001292982.1; NM_001306053.1. DR RefSeq; NP_038567.1; NM_013539.2. [O88838-1] DR RefSeq; XP_006505630.1; XM_006505567.3. [O88838-1] DR PDB; 2AFJ; NMR; -; A=12-224. DR PDB; 3EK9; X-ray; 2.60 A; A=12-224. DR PDBsum; 2AFJ; -. DR PDBsum; 3EK9; -. DR SMR; O88838; -. DR BioGrid; 200055; 1. DR DIP; DIP-29001N; -. DR IntAct; O88838; 2. DR STRING; 10090.ENSMUSP00000060124; -. DR ChEMBL; CHEMBL3325309; -. DR PhosphoSitePlus; O88838; -. DR MaxQB; O88838; -. DR PaxDb; O88838; -. DR PRIDE; O88838; -. DR Antibodypedia; 11257; 92 antibodies. DR DNASU; 14794; -. DR Ensembl; ENSMUST00000047760; ENSMUSP00000041585; ENSMUSG00000038451. [O88838-1] DR Ensembl; ENSMUST00000052727; ENSMUSP00000060124; ENSMUSG00000038451. [O88838-1] DR Ensembl; ENSMUST00000112473; ENSMUSP00000108092; ENSMUSG00000038451. [O88838-2] DR GeneID; 14794; -. DR KEGG; mmu:14794; -. DR UCSC; uc009drw.1; mouse. [O88838-1] DR CTD; 84727; -. DR MGI; MGI:1315199; Spsb2. DR eggNOG; KOG3953; Eukaryota. DR eggNOG; ENOG410XQC1; LUCA. DR GeneTree; ENSGT00950000182795; -. DR InParanoid; O88838; -. DR KO; K10344; -. DR OMA; HAWEIGW; -. DR OrthoDB; 938259at2759; -. DR PhylomeDB; O88838; -. DR TreeFam; TF312822; -. DR Reactome; R-MMU-8951664; Neddylation. DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR UniPathway; UPA00143; -. DR ChiTaRS; Nabp1; mouse. DR EvolutionaryTrace; O88838; -. DR PRO; PR:O88838; -. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; O88838; protein. DR Bgee; ENSMUSG00000038451; Expressed in submandibular gland and 187 other tissues. DR ExpressionAtlas; O88838; baseline and differential. DR Genevisible; O88838; MM. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IBA:GO_Central. DR GO; GO:1990756; F:protein binding, bridging involved in substrate recognition for ubiquitination; ISO:MGI. DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR CDD; cd03719; SOCS_SSB2; 1. DR InterPro; IPR001870; B30.2/SPRY. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR001496; SOCS_box. DR InterPro; IPR036036; SOCS_box-like_dom_sf. DR InterPro; IPR003877; SPRY_dom. DR InterPro; IPR037340; SSB2_SOCS. DR Pfam; PF07525; SOCS_box; 1. DR Pfam; PF00622; SPRY; 1. DR SMART; SM00253; SOCS; 1. DR SMART; SM00969; SOCS_box; 1. DR SMART; SM00449; SPRY; 1. DR SUPFAM; SSF158235; SSF158235; 1. DR SUPFAM; SSF49899; SSF49899; 1. DR PROSITE; PS50188; B302_SPRY; 1. DR PROSITE; PS50225; SOCS; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Reference proteome; KW Ubl conjugation pathway. FT CHAIN 1..264 FT /note="SPRY domain-containing SOCS box protein 2" FT /id="PRO_0000238475" FT DOMAIN 26..221 FT /note="B30.2/SPRY" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548" FT DOMAIN 222..264 FT /note="SOCS box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194" FT VAR_SEQ 222..264 FT /note="VEEPQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLLYK -> GEIRT FT RCGEITTLGNGLGWKLMVGAQEVGFLSLWPVT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_018613" FT MUTAGEN 100..101 FT /note="RG->AA: Loss of interaction with NOS2." FT /evidence="ECO:0000269|PubMed:20603330" FT MUTAGEN 102..103 FT /note="TH->AA: Significant loss of interaction with NOS2." FT /evidence="ECO:0000269|PubMed:20603330" FT MUTAGEN 118..119 FT /note="DH->AA: No loss of interaction with NOS2." FT /evidence="ECO:0000269|PubMed:20603330" FT MUTAGEN 120 FT /note="Y->A: Loss of interaction with PARW. No effect on FT interaction with MET. Loss of interaction with NOS2." FT /evidence="ECO:0000269|PubMed:16369487, FT ECO:0000269|PubMed:20561531, ECO:0000269|PubMed:20603330" FT MUTAGEN 120 FT /note="Y->F: Loss of interaction with NOS2." FT /evidence="ECO:0000269|PubMed:20603330" FT MUTAGEN 123..125 FT /note="LLG->AAA: Loss of interaction with MET and PARW. FT Loss of interaction with NOS2." FT /evidence="ECO:0000269|PubMed:16369487, FT ECO:0000269|PubMed:20561531, ECO:0000269|PubMed:20603330" FT MUTAGEN 126..128 FT /note="SNS->AAA: Loss of interaction with PAWR. Significant FT loss of interaction with NOS2." FT /evidence="ECO:0000269|PubMed:20561531, FT ECO:0000269|PubMed:20603330" FT MUTAGEN 141..143 FT /note="YHQ->AAA: Strongly reduced interaction with MET and FT PARW." FT /evidence="ECO:0000269|PubMed:16369487" FT MUTAGEN 151..152 FT /note="QY->AA: Loss of interaction with MET and PARW." FT /evidence="ECO:0000269|PubMed:16369487" FT MUTAGEN 160..161 FT /note="QL->AA: No loss of interaction with NOS2." FT /evidence="ECO:0000269|PubMed:20603330" FT MUTAGEN 188..189 FT /note="GP->AA: Strongly reduced interaction with MET. Loss FT of interaction with PARW." FT /evidence="ECO:0000269|PubMed:16369487" FT MUTAGEN 198 FT /note="T->A: No loss of interaction with PAWR." FT /evidence="ECO:0000269|PubMed:20561531" FT MUTAGEN 206 FT /note="V->A: Loss of interaction with PARW. No effect on FT interaction with MET. Loss of interaction with NOS2." FT /evidence="ECO:0000269|PubMed:16369487, FT ECO:0000269|PubMed:20561531, ECO:0000269|PubMed:20603330" FT MUTAGEN 207 FT /note="W->A: Significant loss of interaction with NOS2." FT /evidence="ECO:0000269|PubMed:20603330" FT HELIX 29..34 FT /evidence="ECO:0000244|PDB:3EK9" FT HELIX 40..45 FT /evidence="ECO:0000244|PDB:3EK9" FT STRAND 47..53 FT /evidence="ECO:0000244|PDB:3EK9" FT STRAND 57..60 FT /evidence="ECO:0000244|PDB:3EK9" FT HELIX 61..63 FT /evidence="ECO:0000244|PDB:3EK9" FT STRAND 65..68 FT /evidence="ECO:0000244|PDB:3EK9" FT TURN 72..74 FT /evidence="ECO:0000244|PDB:2AFJ" FT STRAND 75..81 FT /evidence="ECO:0000244|PDB:3EK9" FT STRAND 84..94 FT /evidence="ECO:0000244|PDB:3EK9" FT HELIX 97..99 FT /evidence="ECO:0000244|PDB:3EK9" FT STRAND 105..109 FT /evidence="ECO:0000244|PDB:3EK9" FT STRAND 116..119 FT /evidence="ECO:0000244|PDB:3EK9" FT STRAND 130..134 FT /evidence="ECO:0000244|PDB:3EK9" FT TURN 135..137 FT /evidence="ECO:0000244|PDB:3EK9" FT STRAND 139..143 FT /evidence="ECO:0000244|PDB:3EK9" FT STRAND 150..153 FT /evidence="ECO:0000244|PDB:2AFJ" FT HELIX 157..160 FT /evidence="ECO:0000244|PDB:2AFJ" FT STRAND 165..172 FT /evidence="ECO:0000244|PDB:3EK9" FT TURN 173..176 FT /evidence="ECO:0000244|PDB:3EK9" FT STRAND 177..182 FT /evidence="ECO:0000244|PDB:3EK9" FT STRAND 185..191 FT /evidence="ECO:0000244|PDB:3EK9" FT STRAND 199..205 FT /evidence="ECO:0000244|PDB:3EK9" FT STRAND 212..218 FT /evidence="ECO:0000244|PDB:3EK9" SQ SEQUENCE 264 AA; 28938 MW; E71985597D9B38CB CRC64; MGQTALARGS SSTPTSQALY SDFSPPEGLE ELLSAPPPDL VAQRHHGWNP KDCSENIDVK EGGLCFERRP VAQSTDGVRG KRGYSRGLHA WEISWPLEQR GTHAVVGVAT ALAPLQADHY AALLGSNSES WGWDIGRGKL YHQSKGLEAP QYPAGPQGEQ LVVPERLLVV LDMEEGTLGY SIGGTYLGPA FRGLKGRTLY PSVSAVWGQC QVRIRYMGER RVEEPQSLLH LSRLCVRHAL GDTRLGQIST LPLPPAMKRY LLYK //